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(Circulation. 2007;116:25-31.)
© 2007 American Heart Association, Inc.

Coronary Heart Disease

Coronary Artery Calcification Progression Is Heritable

Andrea E. Cassidy-Bushrow, PhD, MPH; Lawrence F. Bielak, DDS, MPH; Patrick F. Sheedy, II, MD; Stephen T. Turner, MD; Iftikhar J. Kullo, MD; Xihong Lin, PhD; Patricia A. Peyser, PhD

From the Department of Epidemiology, University of Michigan, Ann Arbor (A.E.C.-B., L.F.B., P.A.P.); Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Mich (A.E.C.-B.); Department of Diagnostic Radiology (P.F.S.), Division of Hypertension, Department of Internal Medicine (S.T.T.), and Division of Cardiovascular Diseases (I.J.K.), Mayo Clinic and Foundation, Rochester, Minn; and Department of Biostatistics, Harvard University, Boston, Mass (X.L.).

Correspondence to Patricia A. Peyser, PhD, Department of Epidemiology, University of Michigan, 611 Church St, Ann Arbor, MI 48104-3028. E-mail ppeyser{at}umich.edu

Received August 22, 2006; accepted May 8, 2007.

Background— Coronary artery calcification (CAC), a marker of coronary artery atherosclerosis, can be measured accurately and noninvasively with the use of electron beam computed tomography. Serial measures of CAC quantify progression of calcified coronary artery plaque. Little is known about the role of genetic factors in progression of CAC quantity.

Methods and Results— We quantified the relative contributions of measured risk factors and unmeasured genes to CAC progression measured by 2 electron beam computed tomography examinations an average of 7.3 years apart in 877 asymptomatic white adults (46% men) from 625 families in a community-based sample. After adjustment for baseline risk factors and CAC quantity, the estimated heritability of CAC progression was 0.40 (P<0.001). Baseline risk factors and CAC quantity explained 64% of the variation in CAC progression. Thus, genetic factors explained 14% of the variation [(100–64)x(0.40)] in CAC progression. After adjustment for risk factors, the estimated genetic correlation (pleiotropy) between baseline CAC quantity and CAC progression was 0.80 and was significantly different than 0 (P<0.001) and 1 (P=0.037). The environmental correlation between baseline CAC quantity and CAC progression was 0.42 and was significantly different than 0 (P=0.006).

Conclusions— Evidence was found that many but not all genetic factors influencing baseline CAC quantity also influence CAC progression. The identification of common and unique genetic influences on these traits will provide important insights into the genetic architecture of coronary artery atherosclerosis.

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